title: Blockade of CD27/CD70 pathway to reduce the generation of memory T cells and markedly prolong the survival of heart allografts in presensitized mice.
abstract: BACKGROUND
  Alloreactive memory T cells are a major obstacle to transplantation acceptance due to their capacity for accelerated rejection.
  
  
  METHODS
  C57BL/6 mice that had rejected BALB/c skin grafts 4 weeks earlier were used as recipients. The recipient mice were treated with anti-CD154/LFA-1 with or without anti-CD70 during the primary skin transplantation and anti-CD154/LFA-1 or not during the secondary transplantation of BALB/c heart. We evaluated the impact of combinations of antibody-mediated blockade on the generation of memory T cells and graft survival after fully MHC-mismatched transplantations.
  
  
  RESULTS
  One month after the primary skin transplantation, the proportions of CD4(+) memory T cells/CD4(+) T cells and CD8(+)memory T cells/CD8(+) T cells in the anti-CD154/LFA-1 combination group were 47.32±4.28% and 23.18±2.77%, respectively. In the group that included anti-CD70 treatment, the proportions were reduced to 34.10±2.71% and 12.19±3.52% (P<0.05 when comparing the proportion of memory T cells between the two groups). The addition of anti-CD70 to the treatment regimen prolonged the mean survival time following secondary heart transplantation from 10days to more than 90days (P<0.001). Furthermore, allogenic proliferation of recipient splenic T cells and graft-infiltrating lymphocytes were significantly decreased. Meanwhile, the proportion of regulatory T cells was increased to 9.46±1.48% on day 100 post-transplantation (P<0.05).
  
  
  CONCLUSIONS
  The addition of anti-CD70 to the anti-CD154/LFA-1 combination given during the primary transplantation reduced the generation of memory T cells. This therapy regimen provided a potential means to alleviate the accelerated rejection mediated by memory T cells during secondary heart transplantation and markedly prolong the survival of heart allografts.
authors.affiliation: Organ Transplantation Institute, Xiamen University, Fujian Province, PR China.
authors.forename: Helong
authors.initials: H
authors.lastname: Dai
authors.forename: Jibing
authors.initials: J
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Shao
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Shuo
authors.initials: S
authors.lastname: Xu
authors.forename: Yuanzheng
authors.initials: Y
authors.lastname: Peng
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lin
authors.forename: Junjie
authors.initials: J
authors.lastname: Xia
authors.forename: Henrik
authors.initials: H
authors.lastname: Ekberg
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.forename: Zhongquan
authors.initials: Z
authors.lastname: Qi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D053282:CD27 Ligand / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002478:Cells, Cultured; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D016027:Heart Transplantation; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D023001:Transplantation Tolerance
chemical_list: D000911:Antibodies, Monoclonal; D053282:CD27 Ligand; D023201:CD40 Ligand